Patients with head and neck cancers, most of which are squamous cell carcinomas (HNSCC), have defects in their immune defenses. Over 65 percent of HNSCC cancers mobilize CD34+ progenitor cells into the peripheral blood and cancer. These CD34+ cells exhibit natural suppressor (NS) activity which blocks autologous T-cell function. Active vitamin D3 metabolites can stimulate these CD34+ NS cells to develop into dendritic cells. The hypothesis of this exploratory clinical study having laboratory correlates is that treatment of HNSCC cancer patients with 25-hydroxyvitamin D3 stimulates differentiation of immune suppressive CD34+ cells into dendritic cells capable of inducing immune reactivity to autologous HNSCC cancer. The rationale for this hypothesis is based on studies showing (i) vitamin D3 can drive CD34+ cells of HNSCC patients to differentiate in vitro into dendritic cells, (ii) vitamin D3 reduces CD34+ NS levels in tumor-bearing mice and induces immune stimulatory dendritic cells, and (iii) dendritic cells are potent inducers of T-cell reactivity to tumor. The applicant's hypothesis will be tested with peripheral blood and cancer biopsies from HNSCC patients receiving treatment for 6 weeks with 20, 40, 60, or 80 mg 25-hydroxyvitamin D3. The Specific Aims that will test this study's hypothesis are: (i) to drive differentiation of immune suppressive CD34+ cells of HNSCC patients into dendritic cells using 25-hydroxyvitamin D3 treatment, (ii) to demonstrate that 25-hydroxyvitamin D3 treatment to drive differentiation of CD34+ NS cells into dendritic cells induces the appearance of T-cells that are reactive to autologous HNSCC cancer. Upon completion, these studies will show if vitamin D3 treatment of patients whose cancers mobilize CD34+ NS cells will induce dendritic cells capable of stimulating immune reactivity to autologous cancer.